title: Palmitic acid increases medial calcification by inducing oxidative stress.
abstract: BACKGROUND
  Aortic medial calcification is a cellular-regulated process leading to arterial stiffness. Although epidemiological studies have suggested an association between the saturation of fatty acids (FA) and arterial stiffness, there is no evidence that saturated FA can induce arterial calcification. This study investigated the capacity of palmitic acid (PA) to induce medial calcification and the signaling pathway(s) implicated in this process.
  
  
  METHODS
  Rat aortic segments and vascular smooth muscle cells (VSMC) were exposed to calcification medium supplemented with PA. In vivo, rats were treated with warfarin to induce calcification and fed a PA-enriched diet.
  
  
  RESULTS
  In vitro and ex vivo, palmitate increases calcification and ROS production. Palmitate increases extracellular-signal-regulated kinase (ERK1/2) phosphorylation and osteogenic gene expression. Inhibition of NADPH oxidase with apocynin or an siRNA prevents these effects. ERK1/2 inhibition attenuates the amplification of osteogenic gene expression and calcification induced by palmitate. In vivo, a PA-enriched diet amplified medial calcification and pulse wave velocity (PWV). These effects are mediated by ROS production as indicated by the inhibition of calcification and PWV normalization in rats concomitantly treated with apocynin.
  
  
  CONCLUSIONS
  ROS induction by palmitate leads to ERK1/2 phosphorylation and subsequently induces the osteogenic differentiation of VSMC. © 2013 S. Karger AG, Basel.
authors.affiliation: Laboratoire de Pharmacologie Vasculaire, Faculté de Pharmacie, Université de Montréal, Montréal, Qué., Canada.
authors.forename: Mathieu R
authors.initials: MR
authors.lastname: Brodeur
authors.forename: Céline
authors.initials: C
authors.lastname: Bouvet
authors.forename: Mathieu
authors.initials: M
authors.lastname: Barrette
authors.forename: Pierre
authors.initials: P
authors.lastname: Moreau
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002114:Calcinosis / Q000209:etiology; D054338:Cell Transdifferentiation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects*; D019308:Palmitic Acid / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D061205:Vascular Calcification; D014859:Warfarin / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D017382:Reactive Oxygen Species; D019308:Palmitic Acid; D014859:Warfarin; C056165:acetovanillone; D019255:NADPH Oxidases; D048049:Extracellular Signal-Regulated MAP Kinases